We have studied the effects of Pb on the immature rat brain as a model for effects on the human fetus and young child. Maternal Pb feedings, starting when litters are between 1-14 days old, produce an encephalopathy, pathologically like human Pb encephalopathy, in the suckling pup by the third week of feedings. Early in the development of this encephalopathy, Pb feedings produce changes in brain mitochondrial respiration. Cerebral mitochondria show respiratory inhibition in the first two weeks of Pb feedings in animals fed from birth while cerebellar mitochondria are uncoupled and then inhibited in animals fed from two weeks. There may be similar age-dependent regional differences in Pb effects in the human. We have shown also that Pb directly produces similar effects on isolated rat brain mitochondrial respiration in vitro: increased respiration at low concentrations and inhibition of both Pb-induced and ADP-dependent respirations at higher concentrations. However, these in vitro effects did not show the age or regional specificity seen with Pb feedings. We hypothesize that these in situ age and regional specificities may be due to age and regional differences in mitochondrial Pb concentrations and/or to maturation of brain mitochondrial resistance to metabolic effects of altered ambient osmolarity which we have recently demonstrated. Proposed studies for the next year include effects of esophageal catheter Pb feedings, which produce no decrease in weight gain, to determine the role of malnutrition in Pb encephalopathy; regional and age differences in subcellular distribution of Pb and presence of edema as a result of Pb feedings via catheter or via maternal feedings; further in vitro UV-vis absorption spectroscopic study of effects of chronic Pb feedings and acute in vitro exposure to Pb salts on brain mitochondrial respiratory chain cytochrome content. BIBLIOGRAPHIC REFERENCS: Holtzman, D. and Magruder, C.S. (1977) Effects of oligomycin on respiration in developing rat brain mitochondria. Brain Research 120: 373-378. Holtzman, D., Hsu, J. Shen, and Mortell, P. (1977) Effects of inorganic lead on isolated rat brain mitochondrial respiration. Pediatric Res. 11:407.